Ocular hypotensive agents are useful in the treatment of a number of various ocular hypertensive conditions, such as post-surgical and post-laser trabeculectomy ocular hypertensive episodes, glaucoma, and as presurgical adjuncts.
Glaucoma is a disease of the eye characterized by increased intraocular pressure. On the basis of its etiology, glaucoma has been classified as primary or secondary. For example, primary glaucoma in adults (congenital glaucoma) may be either open-angle or acute or chronic angle-closure. Secondary glaucoma results from pre-existing ocular diseases such as uveitis, intraocular tumor or an enlarged cataract.
The underlying causes of primary glaucoma are not yet known. The increased intraocular tension is due to the obstruction of aqueous humor outflow. In chronic open-angle glaucoma, the anterior chamber and its anatomic structures appear normal, but drainage of the aqueous humor is impeded. In acute or chronic angle-closure glaucoma, the anterior chamber is shallow, the filtration angle is narrowed, and the iris may obstruct the trabecular meshwork at the entrance of the canal of Schlemm. Dilation of the pupil may push the root of the iris forward against the angle, and may produce pupillary block and thus precipitate an acute attack. Eyes with narrow anterior chamber angles are predisposed to acute angle-closure glaucoma attacks of various degrees of severity.
Secondary glaucoma is caused by any interference with the flow of aqueous humor from the posterior chamber into the anterior chamber and subsequently, into the canal of Schlemm. Inflammatory disease of the anterior segment may prevent aqueous escape by causing complete posterior synechia in iris bombe, and may plug the drainage channel with exudates. Other common causes are intraocular tumors, enlarged cataracts, central retinal vein occlusion, trauma to the eye, operative procedures and intraocular hemorrhage.
Considering all types together, glaucoma occurs in about 2% of all persons over the age of 40 and may be asymptotic for years before progressing to rapid loss of vision. In cases where surgery is not indicated, topical β-adrenoreceptor antagonists have traditionally been the drugs of choice for treating glaucoma.
In addition, the ability of a compound to exist in more than one crystalline structure or form is known as polymorphism. Many compounds may exist unexpectedly as polymorph crystals and those compounds may also exist in a solid amorphous state. However, the current knowledge and understanding of polymorphism is still such that there is no reasonable degree of predictability with respect to what crystalline forms of the compound might exist and how to make possible unknown polymorphs or other crystalline forms.
Solid state forms of compounds, crystalline or amorphous forms, can be analyzed by one or more solid state analytical methods. Those methods include, for example, X-ray powder diffraction, differential scanning calorimetry, and thermogravimetric analysis.
The solid state forms may be characterized according to X-ray powder diffraction. However, it is known in the art that the measured peaks in the X-ray powder diffractogram of a solid form may vary, because of, for example, different experimental conditions and/or preferred orientations. And according to the instrument precision, the measurement error of 2θ value is generally at ±0.2° (2θ). Moreover, relative intensities have been recognized as non-characteristic for a particular solid form (See Bhattacharya et al., “Polymorphism in Pharmaceutical Solids,” p. 334, 2009.)
Therefore, there is a need for compounds, such as the complex comprising (Z)-7-((1R,2R,3R,5 S)-2-((S,E)-5-(2,5-dichlorothiophen-3-yl)-3-hydroxypent-1-en-1-yl)-3,5-dihydroxycyclopentyl)hept-5-enamide (hereinafter “Compound 1”) and γ-cyclodextrin described herein, for the treatment of ophthalmic diseases such as glaucoma, and for related compositions and methods.